rs32209
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBA1
The NM_001999.4(FBN2):āc.6931A>Gā(p.Met2311Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0751 in 1,613,694 control chromosomes in the GnomAD database, including 12,708 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Consequence
NM_001999.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -19 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FBN2 | NM_001999.4 | c.6931A>G | p.Met2311Val | missense_variant | 55/65 | ENST00000262464.9 | |
FBN2 | XM_017009228.3 | c.6778A>G | p.Met2260Val | missense_variant | 54/64 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FBN2 | ENST00000262464.9 | c.6931A>G | p.Met2311Val | missense_variant | 55/65 | 1 | NM_001999.4 | P1 | |
FBN2 | ENST00000703783.1 | n.3715A>G | non_coding_transcript_exon_variant | 30/38 |
Frequencies
GnomAD3 genomes AF: 0.117 AC: 17723AN: 152100Hom.: 2074 Cov.: 33
GnomAD3 exomes AF: 0.112 AC: 28018AN: 251276Hom.: 4642 AF XY: 0.109 AC XY: 14771AN XY: 135792
GnomAD4 exome AF: 0.0707 AC: 103374AN: 1461476Hom.: 10631 Cov.: 32 AF XY: 0.0718 AC XY: 52216AN XY: 727074
GnomAD4 genome AF: 0.117 AC: 17748AN: 152218Hom.: 2077 Cov.: 33 AF XY: 0.121 AC XY: 9022AN XY: 74416
ClinVar
Submissions by phenotype
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 04, 2013 | Met2311Val in exon 55 of FBN2: This variant is not expected to have clinical sig nificance because it has been identified in 20.7% (914/4406) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http ://evs.gs.washington.edu/EVS; dbSNP rs32209). - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 13, 2012 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Aug 15, 2013 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 22, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Mar 22, 2017 | Variant summary: The FBN2 c.6931A>G (p.Met2311Val) variant involves the alteration of a conserved nucleotide, resulting in a missense substitution. 3/3 in silico tools predict a benign outcome for this variant (SNPs&GO and Mutation Taster not captured due to low reliability index and p-value, respectively). This variant was found in the large control database ExAC at a frequency of 0.1151322 (13966/121304 control chromosomes [2250 homozygotes]), which is approximately 92106 times the estimated maximal expected allele frequency of a pathogenic FBN2 variant (0.0000013), suggesting this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. To our knowledge, the variant of interest has not been reported in affected individuals via publications, nor has it been evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign. - |
Congenital contractural arachnodactyly Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
Familial thoracic aortic aneurysm and aortic dissection Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 24, 2014 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at